NURS 305 Test 1 Liberty University

Sulfonamides

MOA: Inhibits synthesis of bacterial folic acid - bacteriostatic (host defenses needed)

**Trimethoprim/Sulfamethoxazole = TMP/SMX (Bactrim --> inexpensive)

Silver Sulfadiazine (Sivadene) - topical for burns

Sulfacetamide - eye infections

Broad spectrum: Gram pos AND gram neg

Sulfonamides

MAJOR DRUG INTERACTION WITH COUMADIN (increases effects)

Sulfonamides

Used in:

-UTI (E.coli)

-Acute/Chronic cystitis

-Bronchitis

-Acute otitis media in children

-Toxoplasmosis and malaria

-Trachoma

-Topical for burns

-P. jiroveci (pneumocystis pneumonia in AIDS/organ transplant)

Sulfonamides

Adverse effects/Contraindications:

-GI side effects common

-Hypersensitivity (rash, photosensitivity, drug fever, Stevens Johnson syndrome)

-Renal failure due to crystalluria

-Kernicterus in newborns (deposition of bilirubin in brain)

-Hemolytic Anemia (African American and Mediterraneans) - G-6-PD deficiency - fever/pallor/jaundice

-pregnancy/newborns, 1st trimester, end term, nursing, infants

Nitrofurantoin

Bacteristatic by damaging DNA, broad spectrum

Used ONLY for uncomplicated UTI, therapeutic levels only reached in urine. (Staph, Strep, Neisseria, Bacteroides, E.coli, Proteus, Pseudomonas, Enterobacter, Klebsiella)

GI upset common. (Take with milk or meals.) Pulmonary reaction - dyspnea, chest pain, chills, fever, cough. Irreversible peripheral neruopathy, hepatotoxicity, reversible CNS effects.

Not for pt with renal impairment.

Pyridium

Analgesic for UTI - NOT antibiotic!

Treats pain

Causes red discoloration of urine and sweat

Acute Cystitis

First line:

Trimethoprim/sulfamethoxazole (TMP/SMX)

Trimethoprim

Nitrofurantoin

Ciprofloxacin

Norfloxacin

Levofloxacin

Second line:

Nitrofurantoin

Fosfomycin

Acute Uncomplicated pyelonephritis

First line:

Trimethoprim/sufamethoxazole (TMP/SMX)

Trimethoprim

Ciprofloxacin

Levofloxacin

Second Line:

Amoxicillin w/ clavulanic acid

Cephalexin

Cefotaxime

Ceftriaxone

Complicated UTI

Treatment for ________:

Trimethoprim/sulfamethoxazole (TMP/SMX)

Norfloxacin

Ciprofloxacin

Levofloxacin

Amoxicillin w/ clavulanic acid

Cephalexin

Prophylaxis of recurrent UTI

Trimethoprim/sulfamethoxazole (TMP/SMX)

Trimethoprim

Nitrofurantoin

Norfloxacin

Uncomplicated

UTI in women of child-bearing age, no particular predisposing factor, mostly E.coli

Complicated

UIT in men or women associated with some predisposing factor (calculi, prostatic hypertrophy, indwelling catheter, impediment of flow)

Bacteria: E.coli, Klebsiella, Proteus, Pseudomonas, Staph aureus, Enterobacter, Serratia, Candida

Fluroquinolones

MOA: Inhibits bacterial DNA gyrase and topoisomerase IV - bactericidal

Route: IV/PO

**Ciprofloxacin (Cipro)

**Levofloxacin (Levaquin)

Monofloxacin (Avelox)

Gatifloxacin (Tequin) -- pulled from market b/c liver toxicity

Gemifloxaxin (Factive) -- new

Broad spectrum - NOT anaerobes

Respiratory

Use for Levofloxacin, Moxifloxacin, Gatifloxacin

Gram negative

Use for Ciprofloxacin, Levofloxacin (nosocomial pneumonia)

Fluroquinolones

Use: respiratory infections

GU/GI infections

Intra-abdominal infection

Bones, skin, soft tissue

Mutli-drug resistant TB

Antrax

Toxicity:

-CNS - dizziness, confusion, headache

-GI upset

-photosensitivity

-tendon rupture (high risk: 60+, glucocorticoids, organ transplant)

-QT interval prolongation (esp. w/ cardiac drugs like digoxin)

Contraindications:

-children, pregnant/breastfeeding

-don't give w/ Ca, Mg, Zn, multivitamins

Drug interactions:

-avoid antacits, dairy products

-can interact with Coumadin

Metronidazole

MOA: inhibits nucleic acid synthesis - bacteriostatic

Use: Anaerobes only (C.dif, B.fragilis)

-pseudomembranous colitis

-prophylaxis for surgery

-H.pylori infections

Adverse effects

-N/V, diarrhea, CNS effects

Daptomycin

1st drug in class Cyclic lipopeptide

MOA: Penetrates cell membrane, loss in intracellular ions inhibits DNA/RNA/protein synthesis - bacteriocidal

Use: All gram positive (including MRSA)

-Bloodstream infection, complicated skin/skin structure infection

-No drug interactions

Toxicity: Muscle injury (monitor creatine phosphokinase levels)

Given once daily IV, no lab work needed

Mycobacteria

Treatment:

slow growing microbes

requires prolonged treatment =

drug toxicity/poor pt adherence &

promotes emergence of drug-resistance

Tuberculosis

Infection always treated with 2+ drugs

Direct observation of drug administration is standard care

Treatment effective when no mycobacteria in sputum and no colonies in culture

multidrug resistant

TB resistant to isoniazid and rifampin

Extensively drug resistant

TB resistant to Isoniazid and rifampin

All fluoroquinolones

At least one of the injectable second line drugs

Tuberculosis

First line drugs:

Isoniazid, rifampin

Rifapentine, fifabutin, pyrazinamide, ethambutol

Second line drugs:

Levofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, streptomycin, paraaminosalicylic acid, ethionamide, cycloserine

Isoniazid

1st line drug for TB

MOA: inhibits mycolic acid, highly selective for M. tuberculosis. Bactericidal when actively dividing, bacteriostatic to "resting" organisms.

Route: PO/IM

Toxicity:

Peripheral neuropathy (reverse w/ Pyidoxine)

Hepatotoxicity (toxic metabolite, baseline LFT and monitor)

CNS (seizure/dizziness), anemia, GI upset, depression, dry mouth

Drug interaction: Strong inhibitor of CYP2C9, CYP2C19, and CYP2E1 pathways

Rifampin

First line TB drug (equal to Isoniazid)

MOA: suppresses RNA/protein synthesis - bactericidal

Toxicity:

Hepatotoxicity (elevated LFT)

Discoloration of Body fluids - red/orange

GI upset

Cutaneous flushing/itching

Strong inducer (accelerates metabolism of other drugs) - induces cytochrome P450 enzymes

Also used for prophylaxis of meningitis

Rifabuten

1st line drug for TB

MOA: inhibits DNA/RNA/protein synthesis

Route: PO

Toxicity: Rash, GI upset, hepatotoxicity, red discoloration of body fluids

Mild inducer of cytochrome P450 enzymes (dec levels of birth control and delavirdine)

Pyrazinamide

1st line TB drug

MOA: unknown, bactericidal

Use with Isoniazid and Rifampin

Toxicity: Hepatotoxicity (LFT), nongouty parathralgias (pain in multiple joints), hyperuricemia, GI disturbance, photosensitivity

Ethambutol

1st line TB drug, used in strains resistant to Isoniazid and Rifampin

MOA: suppress mycolic acid - bacteriostatic

Route: PO

Toxicity: Optic neuritis - dose related (baseline and monthly visual acuity color testing, blurred vision, constriction of visual field, color disturbance)

-Allergic reaction

-GI upset

-Confusion

-half life doubles in pts with renal insufficiency

Amphotericin B

Class: polyene antibiotics

MOA: Binds to fungal cell membrane, fungistatic or fungicidal depending on concentration

Use: Used in severe systemic fungal infections

Toxicity: Infusion reaction, Nephrotoxicity (extreme! keep pt well hydrated), hypokalemia, hypomagnesemia, myelosuppression

Has decreased incidence of fatal systemic fungal infections

Treat 6weeks-4mos.

Infusion reaction

Occurs in Amphotericin B (nicknamed Ampoterrible b/c this)

-fever, chills, rigors, nausea, headache

-caused by release of proinflammatory cytokines

-symptoms begin 1-3 hours after start of infusion, last an hour

-Less intense w/ lipid based formulations

-Pretreat w/ diphenhydramine/acetaminophen (aspirin can help, increases renal damage)

-IV meperidine or dantrolene can be given if rigors occur

-hydrocortisone given with caution

-amphotericin infusion produces high incidence of phlebitis (change site often, administer through large central vein, pretreat with heparin)

Itraconazole

Class: Azole Antifungal

MOA: Inhibits synthesis of ergosterol

Use: Systemic mycoses (alternative to amphotericin B)

Toxicity: inhibits CYP3A4 pathway, increases levels of other drugs. Cardiosuppression, Liver damage, N/V, diarrhea

Needs acidic environment (antacids, histamine2 antagonists, and proton pump inhibitors reduce absorption of PO med)

Azole Antifungals

What class increases levels of:

Pimozide - antipsychotic - fatal dysrhytmias

Dofetilide - antidysrhythmic - fatal dysrhytmias

Quinidine - Antidysrhythmic - fatal dysrhytmias

Cisapride - Prokinetic agent - fatal dysrhytmias

Warfarin - Anticoagulant - bleeding

Sulfonylureas - oral hypoglycemic - hypoglycemia

Phenytoin - antiseizure - CNS toxicity

Cyclosporine - immunosuppressant - inc. neprhotoxicity

Tacrolimus - immunosuppressant - inc. nephrotoxicity

Lovastatin - antihyperlipidemic - rhabdomyolysis

Simvastatin - antihyperlipidemic - rhabdomyolysis

Eletriptan - antimigraine - coronary vasospasm

Fentanyl - opiod analgesic - fatal respiratory depression

Calcium channel blockers - cardiosuppression

Fluconazole

Class: Azole antifungal

MOA: Inhibits synthesis of ergosterol, fungistatic

Use: Blastomycosis, histoplasmosis, Cryptococcus neoformans, Coccidioides immitis, Candida

Route: PO/IV (dosage/absorption same)

Toxicity: N/V, Headache, abdominal pain, diarrhea

Voriconazole

Class: Azole antifungal

MOA: Suppresses ergosterol synthesis (critical component of fungal membrane) - broad spectrum

Route: IV/PO

Use: Candidemia, invasive aspergillosis (drug of choice), esophageal candidiasis, Scedosporium infections that are resistant.

Toxicity: Hepatotoxicity, visual disturbances, hallucinations, change in color perception (photopsia), teratogenicity, hypersensitivity, N/V and abdominal pain, headache

Drug interactions: cytochrome P450 involvement

Ketoconazole

Class: Azole antifungal

MOA: Inhibits ergosterol

Use: Alternative to amphotericin B for systemic mycoses (less toxic, only somewhat less effective, slower effects, more useful in chronic than acute infections)

Toxicity: GI (reduce by giving with food)

Hepatotoxicity (rare but potentially fatal)

Effect on sex hormones (inhibit steroid synthesis - gynecomastia)

Rash, itching, dizziness, fever, chills, constipation, diarrhea, photophobia, headache

NEEDS ACIDIC ENVIRONMENT - don't give with anything that dec. stomach acid

Posaconazole

Class: Azole antifungal (newest member)

MOA: binds w/ ergosteral in fungal membrane, compromising integrity

Use: Aspergillus and Candida

Toxicity: Typically mild. N/V, headache. Liver injury. QT prolongation and dysrhytmias.

Echinocandins

Drugs:

Caspofungin

Micafungin

Anidulafungin

MOA: Inhibits synthesis of fungal cell walls

Use: systemic infections only: Aspergillus and candida, alternative to Ampho B

IV only

Toxicity: Fever, phlebitis, headache, rash, N/V, histamine reaction

Flucytosine

Class: Pyrimidine analog

MOA: Converted to flurouracil in cells (antimetabolite)

Use: Candida and Cryptococcus neoformans - narrow spectrum. Given w/ Ampho B

Route: PO

Toxicity: Myelosuppression, hepatotoxicity

Nystatin

Class: Polyene Antibiotic

Use: Oral/skin candidiasis

Toxicity: No absorption from PO/topical (suck on oral wafers for oral infection). N/V/D.

Virus

Parasite that can only reproduce inside a living cell

-Difficult to treat

-Antimicrobials are not effective

Acyclovir

Class: Antiviral

MOA: DNA polymerase inhibitor

Route: PO/IV/topical

Use: Herpes simplex, varicella zoster

Toxicity: Generally well tolerated. Phlebitis, Neprhotoxicity - renal failure (IV), N/V/D (oral)

Ganciclovir

Class: Antiviral

MOA: DNA polymerase inhibitor

Use: prevention/treatment of CMV and herpes infection in immunocompromised host

Toxicity: Myelosuppression, teratogenic, CNS, nausea, fever, rash

Famciclovir

Class: Antiviral

MOA: DNA polymerase inhibitor

Use: Herpes zoster, genital herpes

Toxicity: well tolerated

Valacyclovir

Class: Antiviral

MOA: DNA polymerase inhibitor

Use: Prodrug of Acyclovir

Toxicity: well tolerated. Nausea, vomiting, diarrhea, headache, vertigo. (Do not use in immunocompromised pts - causes thrombotic thrombocytopenic purpura/hemolytic uremic syndrome = deadly)

Influenza

Primarily managed by vaccine, changes on a yearly basis (SHOULD BE GIVEN to everyone over 6mos).

Can be inactivated (IM) or live virus (nasal).

Protection begins 1-2 weeks after vaccination, lasts 6 months

Small risk for Guillain-Barre syndrome

Type A virus and type B (type A more common)

Amantadine

Class: Adamantane

MOA:

Use: Type A influenza (NOT used much anymore)

Toxicity: CNS (10-30% of pts, esp. elderly), CHF, orthostatic hypotension)

Oseltamivir

Class/MOA: Neuraminidase inhibitor, newly formed viral particles cant bud off from cytoplasmic membrane

Route: oral

Use: Type A and B influenza, treatment and prophylaxis (MUST start w/in 48 hrs of symptoms)

Adverse effects: N/V (give w/ food)

Nevirapine

Class: NNRTI

MOA/Use: Binds to HIV reverse transcriptase and disrupts active center of enzyme

NEVER use alone - w/ other drugs

Adverse effects: Rash (could be stevens johnson syndrome), hepatotoxicity (monitor ALT and AST baseline at 1st and 12th weeks)

Efavirenz

Class: NNRTI

Preferred agent against HIV, CNS side effects

NNRTIs

Nevirapine

**Efavirenz

Etravirine

Delavirdine

Nevirapine

Rilpivirine

Zidovudine

Class: NRTI

MOA/Use - suppress synthesis of viral DNA

Adverse effects: Anemia/neutropenia, lactic acidosis with liver failure, GI upset, CNS- headache, insomnia, confusion

*not used much anymore, still the prototype

NRTIs

Zidovudine

Didanosine

Zalcitabine (withdrawn from market)

Lamivudine (alternative in pregnancy)

Stavudine

Abacavir

Emtricitabine

Tenofovir

Protease Inhibitors

Most effective antiretroviral drugs available

Used in combination with other drugs

General side effects

-hyperglycemia/diabetes

-fat redistribution to abdomen

-hyperlipidemia

-decreased BMD

-increased serum transaminases - inc. ALT and AST

-drug interactions: metabolized by cytochrome P450 - inhibitors retard metabolism and increase levels, P450 inducers reduce levels.

-->Ritonavir boosting - beneficial

Protease Inhibitors

Saquinavir

Indinavir

Ritonavir

Nelfinavir

Amprenavir - withdrawn from market

Fosamprenavir - prodrug

Darunavir

Atazanvir

Raltegravir

Class/MOA: Integrase Inhibitor (integrase is one of three viral enzymes needed for HIV replication)

Use: In combination with other antiretroviral agents to treat adults infected w/ HIV1

Side effects: headache and insomnia (common), hypersensitivity (rare)

Few drug interactions

Low barrier to resistance

Dolutegravir

Class/MOA: Integrase Inhibitor

One pill, once a day

Well tolerated

Few drug interactions

High barrier to resistance

Elvitegravir

Class/MOA: Integrase inhibitor

One pill once a day

Well tolerated

Many drug interactions due to administration with boosting agent

Low barrier to resistance

Maraviroc

CCR5 Antagonist

Binds with CCR5 and blocks viral entry

Most common side effect: cough, diziness, rash

Rare: liver injury, cardiovascular events

Enfuvirtide

Fusion Inhibitor

MOA/Use - blocks entry of HIV into CD4 cells. New drug - use with others

Adverse effects: injection site reaction, pneumonia, must give injections SQ BID